Diacomit safe and effective as add-on therapy in Dravet infants: Study
30-year, real-world study shows starting treatment before age 2 years is beneficial
Diacomit (stiripentol) was safe and clinically effective at reducing seizures when given to infants with Dravet syndrome, ages 2 or younger, according to a 30-year real world study. It also reduced emergency hospitalizations due to long-lasting seizures.
“This 30-year, real-world experience shows that initiating stiripentol before the age of 2 years is highly beneficial for patients with Dravet syndrome,” researchers wrote in “Initiating stiripentol before 2 years of age in patients with Dravet syndrome is safe and beneficial against status epilepticus,” which was published in Developmental Medicine & Child Neurology.
Long-lasting seizures and status epilepticus are hallmark symptoms of Dravet syndrome’s onset and usually begin in the first year of life. They remain at high risk of occurrence during infancy and middle childhood. The seizures are life-threatening and interfere with development, affecting “quality of life, medical needs, ” and families’ economic well-being.
Treatments focus on reducing seizures frequency and duration, and helping prevent and manage status epilepticus. For infants younger than 2, therapies remain limited, however, mainly due to the low frequency of seizures and their severity.
Diacomit, an antiseizure medication marketed by Biocodex, is administered as an add-on therapy to children with Dravet, including infants. Data on its effectiveness in infants younger than 2 is scarce, however, and individual efficacy or safety data are “often incomplete or pooled with those from older children,” the researchers wrote.
In this study, French researchers retrospectively analyzed real-world data of Dravet patients who began Diacomit before they were 2 and were followed for 30 years (1991-2021). Data from 131 patients (59 women, 72 men) collected over four patient databases in France were analyzed.
Analyzing real-world effect of Diacomit
Genetic tests on 68 patients revealed most (94%) had a mutation in the SCN1A gene, the most common gene mutated with Dravet. Most (93%) received triple therapy with Diacomit added to valproate (brand name Depacon, among others) and clobazam (brand name Onfi, among others).
In this study, short-term therapy was defined as being on Diacomit for under six months while long-term therapy was defined as being on it on the last medical visit and younger than age 7.
The first seizure occurred at a mean age of 5.7 months and Diacomit was initiated at a median age of 12.6 months. Long-lasting seizures (over five minutes) were highly predominant at Diacomit’s start, affecting 98% of patients. At short-term treatment (median dose, 50 mg/kg/day), long-lasting seizures — including prolonged tonic clonic seizures (TCS), which involve both muscle stiffening and twitching, and status epilepticus — were significantly reduced.
Specifically, 55% and 61% of patients saw a significant decrease – of at least 50% – in the frequency of prolonged (lasting 5-30 minutes) TCS and status epilepticus, respectively. Additionally, prolonged TCS stopped in 39% of patients and status epilepticus in 55%.
With long-term Diacomit, the frequency of seizures continued to decline, with a minimum of 50% decline in 67% of patients regarding prolonged TCS and 71% on status epilepticus. Also, prolonged TCS stopped in 62% of patients and status epilepticus in 67%.
At short-term treatment, overall TCS frequency was significantly reduced compared with the beginning of the study, but this wasn’t the case with long-term treatment.
Side effects of Diacomit treatment
At the beginning of the study, 91% of patients had been hospitalized at least once. These numbers decreased to 43% and 12% after short- and long-term treatment, respectively.
With long-term treatment, three patients died due to sudden unexpected death in epilepsy while seven patients discontinued treatment — three due to side effects, one due to insufficient effectiveness), and three due to freedom from seizures and an evaluation of possibly withdrawing treatment.
A total of 72 patients (55%) reported at least one side effect attributed to Diacomit, including appetite/loss of weight (21%), sleep disorders (11%), somnolence (11%), agitation/irritability (7%), and hypotonia (decreased muscle tone, 5%).
There were seven cases of neutropenia (lower than normal levels of neutrophils, a type of white blood cell), five cases of low platelets levels, and 10 cases of elevated transaminases with symptoms, suggestive of liver damage. The side effect rate is similar to rates from studies where patients were later treated with Diacomit, the researchers noted.
Side effects were also noted for valproate (significant weight loss and anorexia) and clobazam (agitation and sleep disorders). In most cases, these were resolved by lowering the dose.
The researchers observed that gastrointestinal events increased with higher doses of Diacomit — from 9% (dose range 30-50 mg/kg/day) to 34% (doses over 50mg/kg/day).
The findings support Diacomit’s effectiveness in controlling “prolonged convulsive seizures and status epilepticus, the predominant and most deleterious seizures at this young age, and may therefore prevent mortality related to status epilepticus.”